Development of potent inhibitors of B-Raf kinase

MEDI 353

Jianmei Wei, Johnson & Johnson Pharmaceutical Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121 and Ronald Wolin, Schering-Plough Research Institute, NJ.
The recently approved anti-cancer agent Sorafinib, is a pan-kinase inhibitor used for the treatment of renal cell carcinoma. One of the kinases that Sorafinib affects is B-Raf kinase, an enzyme involved in cell growth and differentiation. Clinically, mutations to this protein have been linked to >60% of observed melanomas. With the availability of the x-ray crystal structure of B-raf kinase, and our interest in identifying a selective inhibitor of this enzyme, we designed a series of diarylimidiazoles and their isosters to interact with both the ATP and allosteric binding domains of the protein in a effort to obtain a selective B-raf inhibitor. The chemistry and the SAR detailing our efforts at discovering novel B-Raf inhibitors with improved activities will be presented.
 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007